Biochemical Characterization Of Alpha-Synuclein Containing Protein Aggregates In A Yeast Model For Parkinson’S Disease

Parkinson’s disease (PD) is a neurological disorder that affects dopaminergic neurons in the midbrain, which causes loss of motor control and muscle spasms in afflicted individuals. Post-mortem examinations of the brains from PD patients yield large aggregates and oligomers of the protein alpha-synuclein within these neurons. These alpha-synuclein aggregates lead to the atrophy of the affected neurons causing the loss of motor control in patients. To investigate possible pathways that can reduce the levels of the alpha-synuclein protein and its aggregated state, a model using Saccharomyces cerevisiae was designed. One pathway we explored was the ubiquitin-proteasome pathway to determine how alterations of this pathway affect levels of alpha-synuclein. We treated alpha-synuclein expressing yeast with MG132, a proteasome inhibitor, and with PR619, a deubiquinating enzyme inhibitor, to determine if the levels of alpha-synuclein differed from control PD yeast. Results indicated that the levels of alpha-synuclein were altered when treated with the inhibitors implicating the enzymes of the ubiquitin-proteasome pathway in alpha-synuclein regulation. These investigations will help elucidate possible measures that could be taken to prevent the buildup of alpha-synuclein in people suffering from PD.